Aminoglutethimide (AG) is an effective chemical ablative form of therapy for metastatic breast cancer in postmenopausal women. Estrogen receptor (ER) status in breast cancer is useful in predicting the response to the hormonal treatments. Of 134 postmenopausal metastatic breast cancer patients treated with AG, ER analysis was done in 63 patients, 52 of whom are now evaluable. ER biopsy was performed prior to AG therapy in 61 patients, but the results were not known to the investigators.
ER value 2 10 fmolimg cytosol protein was considered ER positive (ER+), 4-9.9 fmolimg borderline, and <4 fmolimg ER negative (ER-). In 38 ER+ patients, objective response rate was 50% (three complete response, 16 partial response) and eight stabilization. Median duration of objective response was 15 months. Forty-three percent of the patients with borderline estrogen receptor level responded ohjectively (three partial response) with the median duration of response eleven months. Fourteen percent of ER-patients responded objectively (one complete response). Hence the estrogen receptor level predicts response in ER+ and ER borderline patients treated with AG.
Cancer 45786-791, 1980.
H E ADRENAL G L A N D S have been known to be a
T source of sex steroids since 1945.9 Huggins et al.
in 1951 first reported a beneficial effect of bilateral adrenalectomy resulting in sex steroid deprivation in advanced carcinoma of the breast,'" and a later study on a larger number of patients with adrenalectomy confirmed the beneficial effect.6 Aminoglutethimide was found to cause adrenal insufficiency when it was used as an anticonvulsant. Further investigations revealed that it inhibited conversion of cholesterol to pregnenol ~n e . ~* j The latter is a major precursor of corticosterone, aldosterone, cortisol, estradiol, and testosterone. Aminoglutethimide is also a potent inhibitor of aromatization in the conversion of androstenedione to est r ~n e . ~~, ~
In 1967, aminoglutethimide was first reported to produce dramatic bone pain relief in metastatic breast cancer.' Further trials of aminoglutethimide in From the